So the BBC news reports that I, parent of an autistic child, am an “infection risk,” from a study in the July 1st Brain, Behavior and Immunity on Parental caregivers of children with developmental disabilities mount a poor antibody response to pneumococcal vaccination.”

(Does that mean autism parents are parasites?)

30 parents of children with developmental disabilities and 29 parents of typically developing children completed “standard measures of depression, perceived stress, social support, caregiver burden, and child problem behaviours,” as well as providing a blood sample and being vaccinated with a pneumococcal polysaccharide vaccine. Blood samples were also taken at 1- and 6-month follow-ups and parents of children with developmental disabilities “mounted a poorer antibody response to vaccination than control parents at both follow-ups.”

Study leader Stephen Gallagher [of the University of Birmingham] said low levels of antibodies suggested parents’ ability to fight infection was weaker: “This is a good indication that their immune systems are not functioning efficiently.”

Stress was likely to be responsible for the immune deficiency, he added.

“These parents are sometimes extremely stressed and what they need is appropriate help and training.”

Co-author Dr Anna Phillips said parents caring for these children are “incredibly dedicated” and not in a position to take time off.

With all due respect, can’t say this study’s findings surprised me. While my son, and taking care of him, are not a burden, yes, life is very busy, very hectic and my husband and I are forever scrambling for babysitters etc.—-circumstances that I suspect are the case for many families with autistic children. If the study can help to further arguments for more services like childcare and afterschool care for special needs children, and imagine having someone to watch one’s child, even for an hour or two, if you’re sick or tired and can catch a fraction of forty winks. (Just imagine.)

As for parents of special needs being weakened in their ability to fight infections, all the more argument to take of ourselves.

(A task which, too often, seems the hardest of all.)

Genetic and environmental factors are frequently cited as causes for autism (and, just to be upfront about it, the genetic studies best explain why my son is autistic). Three recent studies suggest that immunological factors ought also to be considered.

Earlier this month, two studies conducted by researchers at the University of California-Davis M.I.N.D. Institute suggested links between autism and mothers’ immune systems. According to one study, some cases of “regressive autism” (in which a child seems to be developing normally and then loses skills and becomes autistic, in contrast to “early onset autism”) may be connected to the immune systems of mothers during pregnancy; researchers hope to further study IgG antibodies as a potential factor for autism (IgG antibodies are responsible for long-term immune system responses to infection and can also contribute to autoimmune diseases such as arthritis, multiple sclerosis and lupus). Another study found that an interaction between fetal brain cells and antibodies in mothers’ blood could be linked to “stereotypies” such as flapping, toe-walking, spinning, and other repetitive behaviors often noted in autistic children.

A third study reported in the February 25th Science Daily has found that mothers of some autistic children may have produced antibodies during pregnancy that affected their fetus’ brain tissue. The antibodies crossed the placenta and may have caused changes that led to autism:

Mostly anecdotal past evidence of immune system involvement has emerged from unusual antibody levels in some autistic children and from postmortem brain tissue studies showing immune abnormalities in areas of the brain. Antibodies are proteins the body makes in response to viruses and bacteria or sometimes mistakenly against its own tissues. Yet, the majority of children with autism have no clinical evidence of autoimmune diseases, which prompted researchers to wonder whether the antibodies transferred from mother to child during pregnancy could interfere with the fetal brain directly.

To test their hypothesis, the research team used a technique called immunoblotting (or Western blot technology), in which antibodies derived from blood samples are exposed to adult and fetal brain tissue to check whether the antibodies recognize and react against specific brain proteins.

Comparing the antibody-brain interaction in samples obtained from 100 mothers of autistic children and 100 mothers of children without autism, researchers found either stronger reactivity or more areas of reactivity between antibodies and brain proteins in about 40 percent of the samples obtained from the mothers of autistic children. Further, the presence of maternal antibodies was associated with so-called developmental regression in children, increasingly immature behaviors that are a hallmark of autism.

While the findings suggest an association between autism and the presence of fetal brain antibodies, the investigators say further studies are needed to confirm that particular antibodies do indeed cross the placenta and cause damage to the fetal brain.

“The mere fact that a pregnant woman has antibodies against the fetal brain doesn’t mean she will have an autistic child,” [Harvey] Singer [M.D., director of pediatric neurology at Johns Hopkins Children's Center] says.

The new study will be published in the February issue of the Journal of Neuroimmunology.

Since these studies connecting maternal antibodies to autism are focused on the immune system of mothers, it will be interesting to see if there is a greater focus on how a mother’s health might affect her fetus and its development, and what this might have to do with autism.

Researchers at the University of California-Davis M.I.N.D. Institute suggest that some cases of “regressive autism”—-in which a child seems to be developing normally and then loses skills and becomes autistic, in contrast to “early onset autism”—-may be connected to the immune systems of mothers during pregnancy. Antibodies in the blood of mothers of autistic children were found to bind with fetal brain cells and affect healthy brain development. More specifics about the study from Science Daily:

[Judy] Van de Water, senior author of the study and professor of rheumatology, allergy and clinical immunology, and her team began their research with blood samples from 123 mothers – 61 whose children have autism and 62 whose children are typically developing. They isolated IgG antibodies from the samples then exposed the antibody to fetal brain tissue by western blot analysis, which detects antibody reactivity to proteins. The outcome revealed a highly specific reactivity pattern to two fetal brain proteins in seven of the 61 samples from the autism group, six of which were from mothers of children who had regressive autism. None of the IgG samples from mothers in the control group produced this same result.

“We’re not entirely sure why the IgG response against fetal brain proteins was so specific for later onset autism,” said Van de Water. “It’s possible that early exposure to maternal antibodies sets in motion a biological path to autism with the behavioral outcomes not apparent until much later. It’s also possible that an environmental exposure sometime after birth could be required to set this process in motion. We are hopeful that this study will help build our understanding of the foundations of the regressive form of the disorder.”

……..

IgG antibodies are responsible for long-term immune system responses to infection, but they can also contribute to autoimmune diseases such as arthritis, multiple sclerosis and lupus. IgG also crosses the placenta in order to provide key immune system protectants to a growing fetus and newborn child, which is a key reason why Van de Water decided to investigate the role of IgG as a potential factor in autism.

Van de Water next wants to know if IgG in women during the time of their pregnancies produces the same response to fetal brain proteins. Women in the current study were two-to-five years beyond childbirth. She will now conduct the same study with women who are pregnant and already have a child with autism, because such women are much more likely to have another child with the disorder.

“If women in this next phase of the study give birth to a child eventually diagnosed with autism, blood analyses from all stages of her pregnancy will give us a clear picture of the immune system factors that were in play during gestation and could have altered her child’s neurodevelopment,” Van de Water said.

Researchers are hopeful that a prenatal test and therapeutic interventions preventing IgG exposure during pregnancy could “protect some children from ever getting autism.” This is the first study to consider the immune systems of mothers of autistic children; a growing number of studies has investigated autistic children’s immune systems. The findings will be published in the March 2008 issue of Neurotoxicology.

Another study conducted by researchers from the M.I.N.D. Institute builds on Van de Water’s research and shows that an interaction between fetal brain cells and antibodies in mothers’ blood could be linked to “stereotypies” such as flapping, toe-walking, spinning, and other repetitive behaviors often noted in autistic children. The study will be published in a future issue of Brain, Behavior, and Immunity. From Science Daily:

[Neuroscientist David] Amaral and his research team at the California National Primate Research Center exposed eight rhesus monkeys to human IgG at three times during the end of the first trimester of pregnancy. Four monkeys received IgG from mothers of children with autism, while four received antibody isolated from the blood of mothers of typically developing children to ensure that any potential outcomes were not due to human IgG exposure. Five monkeys received no treatment whatsoever and were included as study controls. The behavior and social interactions of all 13 offspring were then carefully observed and recorded over the course of a year-and-a-half in a variety of familiar and novel settings.

The team identified only mild social alterations in the four monkeys treated with IgG from mothers of children with autism. The monkeys’ behavior, however, was notably distinct, since all of them exhibited repetitive activities such as pacing, backflipping, twirling and swinging with much greater frequency and for longer periods of time than other monkeys in the study. The stereotypies were most pronounced after weaning and were even more striking in unfamiliar settings.

“The major significance of this study is that it links exposure to abnormal immune system factors during pregnancy with specific behavioral outcomes in offpsring,” said Amaral. “The monkeys’ behavior is profoundly changed from normal, and those changes are similar to impairments that we see in children with autism. The study adds to increasing evidence that immune system factors of mothers could contribute to the development of some forms of autism.”

While the finding is remarkable, the results must be replicated in a larger, more comprehensive study before prenatal IgG exposure can be confirmed as a risk factor for autism. At that point, the researchers are hopeful that clinical protocols can be developed to identify this risk factor during pregnancy.

Such “stereotypies” are only one feature of autism, though they are “part of one major symptom category — in addition to social deficits and language impairments — of the autism diagnosis”; clinicians do not know why autistic persons engage in these behaviors. My own observations of my son Charlie—he does not flap or toe walk, but paces, among other things—are that he performs these behaviors to comfort, calm, and soothe himself; more than a few autistic adults have noted the same.

Researchers note that the study is small and that its results need to be replicated to further investigate if a causal factor for some cases of autism has been discovered. Loren Martin, the lead author of the study and now a professor of psychology at Asuza Pacific University, notes that these findings are still at an “early stage” of being investigated. Treatments like those for used for autoimmune and inflammatory diseases”—such as lupus, arthritis, and multiple sclerosis—-might be developed.

Researchers at the M.I.N.D. Institute at the University of California at Davis are the first to use genomic profiling of blood to note differences in autistic children, the January 25th Health News Digest reports. Their hope is that such “gene expression analyses can provide biological evidence of autism, currently diagnosed only through behavioral assessments, in some children.”

“What we found were 11 specific genes with expression levels that were significantly higher in the blood of children with autism when compared to the blood of typically developing children,” said Frank Sharp, senior author of the study and professor of neurology with the M.I.N.D. Institute. “Those 11 genes are all known to be expressed by natural-killer cells, which are cells in the immune system necessary for mounting a defense against infected cells. We were surprised by our results because we were not looking for these particular genes. And while a number of studies have shown immune system dysregulation to be an important factor in autism, ours is one of the first to implicate these particular cells.”

In conducting the study, Sharp, molecular pathologist Jeff Gregg and their M.I.N.D. Institute colleagues used blood samples from 35 children diagnosed with autism, 14 with development delay but not autism and 12 typically developing children. The samples were subjected to gene expression analysis using microarrays and compared for common patterns. In addition to finding the 11 genes with natural-killer cell connections shared by all of the children with autism, they identified a pattern of 140 genes differentially expressed in children with the early onset form of the disorder and a pattern of 20 genes differentially expressed in children with the regressive form of the disorder. The team is the first to use genomic profiling of blood to observe differences in children with autism.

Might this study point towards the development of a blood test for autism, of a biomarker for diagnosing autism? The study is published in the January issue of Genomics.

Dr. Sharp further notes that the current study also does not “identify whether or not the natural-killer cells are functioning abnormally,” which further work by M.I.N.D. Institute immunologists will consider reveal. He continues:

“If the natural-killer cells are dysfunctional, this might mean that they cannot rid a pregnant mother, fetus or newborn of an infection, which could contribute to autism.”

The image of some “natural killer” cells that ward off tumors and affect cells, and so play a role in the genes of autistic children stands out. One can imagine proponents of theories that something in the environment “triggers” autism making something of this research about something like stealth autism getting into the genes of some children and causing an “infection” in a pregnant mother or fetus.

A life less ordinary by Emily goes into much more detail about this study and about autoimmunity and autism (and I’ll note here that, between Jim’s family and mine, there is a history of autoimmune disorders: multiple sclerosis and allergies on his side, and asthma, which I used to have a severe case of).